Azithromycin-Induced Thrombocytopenia: A Rare Etiology of Drug-Induced Immune Thrombocytopenia.

Drug-induced thrombocytopenia requires a high suspicion for diagnosis and a broad investigation to exclude other etiologies of low platelets. Cessation of the offending agent often results in recovery of platelet counts. Many medications are known to cause a degree of thrombocytopenia. We present a rare case of severe thrombocytopenia associated with administration of azithromycin.

Outcomes of Heart Block in Myocarditis: A Review of 31,760 Patients.

BACKGROUND: Various electrocardiographic abnormalities, including atrioventricular conduction block, have been reported in patients with myocarditis. We performed an observation study to describe the characteristics and outcomes of inpatients diagnosed with myocarditis complicated by heart block (HB) in a large national cohort. METHODS: We identified patients with primary ICD-9 codes for myocarditis HB from the Nationwide Inpatient Sample (NIS) Database from 1998 to 2013. We compared the baseline characteristics and compared clinical outcomes between patients with and without HB, and in patients with/without high degree atrioventricular block (HDAVB). RESULTS: From the NIS database, 31,760 patients had a principal diagnosis of myocarditis and HB was reported in 1.7% of these patients (n=540). Female gender and Asian race were independently associated with HB. Out of 540 patients, 363 patients had HDAVB (67.2%) and 177 patients had not advanced HB (32.8%). Not advanced HB was not associated with an increased mortality rate compared to patients without HB (0% vs. 2.7%, p=0.315). On the other hand, the incidence of cardiogenic shock, respiratory failure and renal failure were higher in patients with HDAVB (26.2% vs. 5.0%, 33.9% vs. 5.9% and 29.2% vs. 5.5%, p<0.001 respectively). Patients with HDAVB required more procedural support (incidence of intra-aortic balloon pump 17.8% vs. 3.3%). They also had significantly longer lengths of hospital stay (9.4±9.4 vs. 4.3±8.4, p<0.001) and higher mortality (15.5% vs. 2.7%, p<0.001). Compared to myocarditis patients without HB, the odds for mortality in myocarditis patients with HDAVB 1.58 (95% CI=1.03-2.49, p=0.039). CONCLUSIONS: The incidence of HB and HDAVB among patients with acute myocarditis was 1.7% and 1.1% respectively. Female gender and Asian race were both independently associated with significant odds for the occurrence of HB and HDAVB. High degree atrioventricular block was independently associated with increased morbidity and mortality.

Functional Invalidation of Putative Sudden Infant Death Syndrome-Associated Variants in the KCNH2-Encoded Kv11.1 Channel.

BACKGROUND: Heterologous functional validation studies of putative long-QT syndrome subtype 2-associated variants clarify their pathological potential and identify disease mechanism(s) for most variants studied. The purpose of this study is to clarify the pathological potential for rare nonsynonymous KCNH2 variants seemingly associated with sudden infant death syndrome. METHODS: Genetic testing of 292 sudden infant death syndrome cases identified 9 KCNH2 variants: E90K, R181Q, A190T, G294V, R791W, P967L, R1005W, R1047L, and Q1068R. Previous studies show R181Q-, P967L-, and R1047L-Kv11.1 channels function similar to wild-type Kv11.1 channels, whereas Q1068R-Kv11.1 channels accelerate inactivation gating. We studied the biochemical and biophysical properties for E90K-, G294V-, R791W-, and R1005W-Kv11.1 channels expressed in human embryonic kidney 293 cells; examined the electronic health records of patients who were genotype positive for the sudden infant death syndrome-linked KCNH2 variants; and simulated their functional impact using computational models of the human ventricular action potential. RESULTS: Western blot and voltage-clamping analyses of cells expressing E90K-, G294V-, R791W-, and R1005W-Kv11.1 channels demonstrated these variants express and generate peak Kv11.1 current levels similar to cells expressing wild-type-Kv11.1 channels, but R791W- and R1005W-Kv11.1 channels accelerated deactivation and activation gating, respectively. Electronic health records of patients with the sudden infant death syndrome-linked KCNH2 variants showed that the patients had median heart rate-corrected QT intervals <480 ms and none had been diagnosed with long-QT syndrome or experienced cardiac arrest. Simulating the impact of dysfunctional gating variants predicted that they have little impact on ventricular action potential duration. CONCLUSIONS: We conclude that these rare Kv11.1 missense variants are not long-QT syndrome subtype 2-causative variants and therefore do not represent the pathogenic substrate for sudden infant death syndrome in the variant-positive infants.

Deep Vein Thrombosis Complicated by Spontaneous Iliopsoas Hematoma in Patient with Septic Shock.

BACKGROUND Spontaneous retroperitoneal hemorrhage (SRH) is a rare and difficult-to-diagnose entity. It is not associated with trauma, pathology, or iatrogenic manipulations. Few cases have been reported, with the only precipitating factor recognized being bleeding diatheses such as anticoagulation states, inherited coagulopathies, and hemodialysis. However, none of these have been described in combination with septic shock, which itself is associated with platelet dysfunction, coagulation dysfunction, and vasculopathy. CASE REPORT Our case involves an elderly man presenting with altered mental status of unknown etiology, in addition to hemodynamic instability, presumably due to septic shock, without any overt signs of bleeding. After his initial exam revealed lower-extremity edema and decubitus ulcers, a venous Doppler was performed, which revealed extensive deep vein thrombosis. It was unknown whether the sepsis or DVT occurred first. Therapeutic anticoagulation with heparin was subsequently started. On hospital day 4, a CT abdomen with contrast identified retroperitoneal hematoma after the patient's hemoglobin lowered without any overt signs of bleeding. The diagnosis of spontaneous retroperitoneal hematoma was one of exclusion and posed a therapeutic dilemma (conservative versus invasive management). CONCLUSIONS Sepsis-related coagulopathy and heparin use in an elderly patient predisposed him to an iliopsoas hematoma. In this case, conservative management with reversal of anticoagulation and blood transfusion was sufficient to stabilize the patient.

QT prolongation is associated with increased mortality in end stage liver disease.

AIM: To determine the prevalence of QT prolongation in a large series of end stage liver disease (ESLD) patients and its association to clinical variables and mortality. METHODS: The QT interval was measured and corrected for heart rate for each patient, with a prolonged QT cutoff defined as QT > 450 ms for males and QT > 470 ms for females. Multiple clinical variables were evaluated including sex, age, serum sodium, international normalized ratio, creatinine, total bilirubin, beta-blocker use, Model for End-Stage Liver Disease (MELD), MELD-Na, and etiology of liver disease. RESULTS: Among 406 ESLD patients analyzed, 207 (51.0%) had QT prolongation. The only clinical variable associated with QT prolongation was male gender (OR = 3.04, 95%CI: 2.01-4.60, P < 0.001). During the study period, 187 patients (46.1%) died. QT prolongation was a significant independent predictor of mortality (OR = 1.69, 95%CI: 1.03-2.77, P = 0.039). In addition, mortality was also associated with viral etiology of ESLD, elevated MELD score and its components (P < 0.05 for all). No significant reversibility in the QT interval was seen after liver transplantation. CONCLUSION: QT prolongation was commonly encountered in an ESLD population, especially in males, and served as a strong independent marker for increased mortality in ESLD patients.

Opioid withdrawal suppression efficacy of oral dronabinol in opioid dependent humans.

BACKGROUND: The cannabinoid (CB) system is a rational novel target for treating opioid dependence, a significant public health problem around the world. This proof-of-concept study examined the potential efficacy of a CB1 receptor partial agonist, dronabinol, in relieving signs and symptoms of opioid withdrawal. METHODS: Twelve opioid dependent adults participated in this 5-week, inpatient, double-blind, randomized, placebo-controlled study. Volunteers were maintained on double-blind oxycodone (30mg oral, four times/day) and participated in a training session followed by 7 experimental sessions, each testing a single oral test dose (placebo, oxycodone 30 and 60mg, dronabinol 5, 10, 20, and 30mg [decreased from 40mg]). Placebo was substituted for oxycodone maintenance doses for 21h before each session in order to produce measurable opioid withdrawal. Outcomes included observer- and participant-ratings of opioid agonist, opioid withdrawal and psychomotor/cognitive performance. RESULTS: Oxycodone produced prototypic opioid agonist effects (i.e. suppressing withdrawal and increasing subjective effects indicative of abuse liability). Dronabinol 5 and 10mg produced effects most similar to placebo, while the 20 and 30mg doses produced modest signals of withdrawal suppression that were accompanied by dose-related increases in high, sedation, bad effects, feelings of heart racing, and tachycardia. Dronabinol was not liked more than placebo, showed some impairment in cognitive performance, and was identified as marijuana with increasing dose. CONCLUSION: CB1 receptor activation is a reasonable strategy to pursue for the treatment of opioid withdrawal; however, dronabinol is not a likely candidate given its modest withdrawal suppression effects of limited duration and previously reported tachycardia during opioid withdrawal.

Safety of oral dronabinol during opioid withdrawal in humans.

BACKGROUND: Opioid dependence remains a significant public health problem worldwide with only three FDA-approved treatments, all targeting the mu-opioid receptor. Dronabinol, a cannabinoid (CB) 1 receptor agonist, is currently under investigation as a novel opioid withdrawal treatment. This study reports on safety outcomes of dronabinol among adults in opioid withdrawal. METHODS: Twelve adults physically dependent on short-acting opioids participated in this 5-week within-subject, randomized, double blind, placebo-controlled inpatient study. Volunteers were maintained on oral oxycodone 30 mg qid. Double-blind placebo substitutions occurred for 21 h before each of 7 experimental sessions in order to produce opioid withdrawal. A single oral test dose was administered each session (placebo, oxycodone 30 and 60 mg, dronabinol 5, 10, 20, and 30 mg [decreased from 40 mg]). Heart rate, blood pressure, respiratory outcomes and pupil diameter were assessed repeatedly. RESULTS: Dronabinol 40 mg produced sustained sinus tachycardia accompanied by anxiety and panic necessitating dose reduction to 30 mg. Sinus tachycardia and anxiety also occurred in one volunteer after dronabinol 20mg. Compared to placebo, dronabinol 20 and 30 mg produced significant increases in heart rate beginning 1h after drug administration that lasted approximately 2h (p<0.05). Dronabinol 5 and 10mg produced placebo-like effects. Oxycodone produced prototypic mu-opioid agonist effects (e.g., miosis). CONCLUSION: Dronabinol 20mg and higher increased heart rate among healthy adults at rest who were in a state of opioid withdrawal, raising concern about its safety. These results have important implications for future dosing strategies and may limit the utility of dronabinol as a treatment for opioid withdrawal.

Cardiovascular regulation during body unweighting by lower body positive pressure.

BACKGROUND: We hypothesized that human cardiovascular responses to standing in reduced gravity environments, as on the Moon or Mars, could be modeled using a lower body positive pressure (LBPP) chamber. METHODS: Heart rate, blood pressure, body segment fluid shifts, ECG, indexes of sympathetic, parasympathetic balance, and baroreflex control of the heart and periphery plus echocardiographic measures of cardiac function were recorded from seven men and seven women supine and standing at 100% (Earth), 40% (-Mars), and 20% (-Moon) bodyweights (BW). RESULTS: The fluid shifted from the chest was greater when standing at 100% BW than at 20% and 40% BW, while fluid pooled in the abdomen was similar at all BWs. Compared to moving from supine to standing at 100% BW, moving to 20% and 40% BW resulted in smaller decreases in stroke volume and pulse pressure, smaller increases in heart rate and smaller decreases in parasympathetic control of heart rate, baroreflex slope, numbers of blood pressure ramps, and much reduced indexes of sympathetic drive to the heart and periphery. However, peripheral vascular resistance, systolic pressure, and baroreflex effectiveness were elevated during 20% and 40% BW, compared to supine and standing at 100% BW. DISCUSSION: Standing at reduced bodyweight suppressed indexes of sympathetic control of heart rate and peripheral vasomotion. Regulatory responses indicated a combination of arterial and cardiopulmonary baroreflex control: mean heart rate, vasomotion, and baroreflex sensitivity appeared to be more under cardiopulmonary control while baroreflex effectiveness appeared to be driven more by the arterial baroreflex.